Here we report that small, physiological elevations of extracellular sodium in cell culture and mild dehydration that elevates plasma sodium in mice activate inflammatory signaling (increased VCAM-1, E-selectin and MCP-1 expression), increase adhesive properties of endothelial cells, and lead to vascular changes that promote atherosclerosis and thickening of walls of coronary arteries. The gene discussed is SELE; the disease is atherosclerosis.